Ratios of T-cell immune-effectors with tumour associated macrophages and PD-1/PD-L1 axis immune-checkpoint molecules, as prognosticators in diffuse large B cell lymphoma: A population-based study

Background Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured despite initial R-CHOP. Although the prognostic importance of the tumour microenvironment (TME) is established, the optimal strategy to quantify it is unknown. Methods The relationship between immune-effector and inhibitory (checkpoint) genes was assessed by NanoString™ in 252 paraffin-embedded DLBCL tissues. A model to quantify net anti-tumoural immunity as an outcome predictor was tested in 158 R-CHOP treated patients, and validated in tissue/blood from two independent R-CHOP treated cohorts of 233 and 140 patients respectively. Findings T and NK-cell immune-effector molecule expression correlated with tumour associated macrophage and PD-1/PD-L1 axis markers consistent with malignant B-cells triggering a dynamic checkpoint response to adapt to and evade immune-surveillance. A tree-based survival model was performed to test if immune-effector to checkpoint ratios were prognostic. The CD4*CD8:(CD163/CD68)*PD-L1 ratio was better able to stratify overall survival than any single or combination of immune markers, distinguishing groups with disparate 4-year survivals (92% versus 47%). The immune ratio was independent of and added to the revised international prognostic index (R-IPI) and cell-of-origin (COO). Tissue findings were validated in 233 DLBCL R-CHOP treated patients. Furthermore, within the blood of 140 R-CHOP treated patients immune-effector:checkpoint ratios were associated with differential interim-PET/CT+ve/-ve expression.

STEM education K-12: perspectives on integration

This commentary was stimulated by Yeping Li's first editorial (2014) citing one of the journal's goals as adding multidisciplinary perspectives to current studies of single disciplines comprising the focus of other journals. In this commentary I argue for a greater focus on STEM integration, with a more equitable representation of the four disciplines in studies purporting to advance STEM learning. The STEM acronym is often used in reference to just one of the disciplines, commonly science. Although the integration of STEM disciplines is increasingly advocated in the literature, studies that address multiple disciplines appear scant with mixed findings and inadequate directions for STEM advancement. Perspectives on how discipline integration can be achieved are varied, with reference to multidisciplinary, interdisciplinary, and transdisciplinary approaches adding to the debates. Such approaches include core concepts and skills being taught separately in each discipline but housed within a common theme; the introduction of closely linked concepts and skills from two or more disciplines with the aim of deepening understanding and skills; and the adoption of a transdisciplinary approach, where knowledge and skills from two or more disciplines are applied to real-world problems and projects with the aim of shaping the total learning experience. Research that targets STEM integration is an embryonic field with respect to advancing curriculum development and various student outcomes. For example, we still need more studies on how student learning outcomes arise not only from different forms of STEM integration but also from the particular disciplines that are being integrated. As noted in this commentary, it seems that mathematics learning benefits less than the other disciplines in programs claiming to focus on STEM integration. Factors contributing to this finding warrant more scrutiny. Likewise, learning outcomes for engineering within K-12 integrated STEM programs appear under-researched. This commentary advocates a greater focus on these two disciplines within integrated STEM education research. Drawing on recommendations from the literature, suggestions are offered for addressing the challenges of integrating multiple disciplines faced by the STEM community.

The Instabooth

The InstaBooth is a portable demountable interactive installation for situated community engagement. Its aim is to give a voice to communities who can share their thoughts and ideas in an unstructured and playful way that combines digital technology with tangible materials. It is constructed from standard CNC-cut plywood stock and plans for its construction are available for others to download and use. Its modular design accommodates a range of bespoke interactive technologies, both analogue and digital, designed to facilitate the engagement process by providing means to present different materials and offer different ways to collect feedback. The appearance and interactions of the booth are designed to appeal to different demographics and foster an interactive discussion about a range of different topics such as change management, policy development, and urban planning.

Changes in cannabis use among psychotic clients without specialised substance use treatment

The need to address substance use among people with psychosis has been well established. However, treatment studies targeting substance use in this population have reported mixed results. Substance users with psychosis in no or minimal treatment control groups achieve similar reductions in substance use compared to those in more active substance use treatment, suggesting a role for natural recovery from substance use. This meta-analysis aims to quantify the amount of natural recovery from substance use within control groups of treatment studies containing samples of psychotic substance users, with a particular focus on changes in cannabis use. A systematic search was conducted to identify substance use treatment studies. Meta-analyses were performed to quantify reductions in the frequency of substance use in the past 30 days. Significant but modest reductions (mean reduction of 0.3–0.4 SD across the time points) in the frequency of substance use were found at 6 to 24 months follow up. The current study is the first to quantify changes in substance use in samples enrolled in no treatment or minimal treatment control conditions. These findings highlight the potential role of natural recovery from substance use among individuals with psychosis, although they do not rule out effects of regression to the mean. Additionally, the results provide a baseline from which to estimate likely changes or needed effects sizes in intervention studies. Future research is required to identify the processes underpinning these changes, in order to identify strategies that may better support self-management of substance use in people with psychosis.

The influence of impurities on calcium phosphate floc structure and size in sugar solutions

Settling, dewatering and filtration of flocs are important steps in industry to remove solids and improve subsequent processing. The influence of non-sucrose impurities (Ca2+, Mg2+, phosphate and aconitic acid) on calcium phosphate floc structure (scattering exponent, Sf), size and shape were examined in synthetic and authentic sugar juices using X-ray diffraction techniques. In synthetic juices, Sf decreases with increasing phosphate concentration to values where loosely bound and branched flocs are formed for effective trapping and removal of impurities. Although, Sf did not change with increasing aconitic acid concentration, the floc size significantly decreased reducing the ability of the flocs to remove impurities. In authentic juices, the flocs structures were marginally affected by increasing proportions of non-sucrose impurities. However, optical microscopy indicated the formation of well-formed macro-floc network structures in sugar cane juices containing lower proportions of non-sucrose impurities. These structures are better placed to remove suspended colloidal solids.

A multi-centre open-label randomised non-inferiority trial comparing watchful waiting to antibiotic treatment for acute otitis media without perforation in low-risk urban Aboriginal and Torres Strait Islander children (the WATCH trial): study protocol for a randomised controlled trial

Background Treatment guidelines recommend watchful waiting for children older than 2 years with acute otitis media (AOM) without perforation, unless they are at high risk of complications. The high prevalence of chronic suppurative otitis media (CSOM) in remote Aboriginal and Torres Strait Islander communities leads these children to be classified as high risk. Urban Aboriginal and Torres Strait Islander children are at lower risk of complications, but evidence to support the subsequent recommendation for watchful waiting in this population is lacking. Methods/Design This non-inferiority multi-centre randomised controlled trial will determine whether watchful waiting is non-inferior to immediate antibiotics for urban Aboriginal and Torres Strait Islander children with AOM without perforation. Children aged 2 − 16 years with AOM who are considered at low risk for complications will be recruited from six participating urban primary health care services across Australia. We will obtain informed consent from each participant or their guardian. The primary outcome is clinical resolution on day 7 (no pain, no fever of at least 38 °C, no bulging eardrum and no complications of AOM such as perforation or mastoiditis) as assessed by general practitioners or nurse practitioners. Participants and outcome assessors will not be blinded to treatment. With a sample size of 198 children in each arm, we have 80 % power to detect a non-inferiority margin of up to 10 % at a significance level of 5 %, assuming clinical improvement of at least 80 % in both groups. Allowing for a 20 % dropout rate, we aim to recruit 495 children. We will analyse both by intention-to-treat and per protocol. We will assess the cost- effectiveness of watchful waiting compared to immediate antibiotic prescription. We will also report on the implementation of the trial from the perspectives of parents/carers, health professionals and researchers. Discussion The trial will provide evidence for the safety and effectiveness of watchful waiting for the management of AOM in Aboriginal and Torres Strait Islander children living in urban settings who are considered to be at low risk of complications.

The influence of the elements of procedural justice and speed camera enforcement on young novice driver self-reported speeding

Road policing is an important tool used to modify road user behaviour. While other theories, such as deterrence theory, are significant in road policing, there may be a role for using procedural justice as a framework to improve outcomes in common police citizen interactions such as traffic law enforcement. This study, using a sample of 237 young novice drivers, considered how the four elements of procedural justice (voice, neutrality, respect and trustworthiness) were perceived in relation to two forms of speed enforcement: point-to-point (or average) speed and mobile speed cameras. Only neutrality was related to both speed camera types suggesting that it may be possible to influence behaviour by emphasising one or more elements, rather than using all components of procedural justice. This study is important as it indicates that including at least some elements of procedural justice in more automated policing encounters can encourage citizen compliance.

The effects of height and BMI on prostate cancer incidence and mortality: A Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium

Background Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality. Methods We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies. Results The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03). Conclusions We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.

Glycaemic behaviour during breastfeeding in women with Type 1 diabetes

Aim To describe glycaemia in both breastfeeding women and artificially feeding women with Type 1 diabetes, and the changes in glycaemia induced by suckling. Methods A blinded continuous glucose monitor was applied for up to 6 days in eight breastfeeding and eight artificially feeding women with Type 1 diabetes 2–4 months postpartum. Women recorded glucose levels, insulin dosages, oral intake and breastfeeding episodes. A standardized breakfast was consumed on 2 days. A third group (clinic controls) were identified from a historical database. Results Carbohydrate intake tended to be higher in breastfeeding than artificially feeding women (P = 0.09) despite similar insulin requirements. Compared with breastfeeding women, the high blood glucose index and standard deviation of glucose were higher in artificially feeding women (P = 0.02 and 0.06, respectively) and in the clinical control group (P = 0.02 and 0.05, respectively). The low blood glucose index and hypoglycaemia were similar. After suckling, the low blood glucose index increased compared with before (P < 0.01) and during (P < 0.01) suckling. Hypoglycaemia (blood glucose < 4.0 mmol/l) occurred within 3 h of suckling in 14% of suckling episodes, and was associated with time from last oral intake (P = 0.04) and last rapid-acting insulin (P = 0.03). After a standardized breakfast, the area under the glucose curve was positive. In breastfeeding women the area under the glucose curve was positive if suckling was avoided for 1 h after eating and negative if suckling occurred within 30 min of eating. Conclusions Breastfeeding women with Type 1 diabetes had similar hypoglycaemia but lower glucose variability than artificially feeding women. Suckling reduced maternal glucose levels but did not cause hypoglycaemia in most episodes.

Protocol for assessing maternal, environmental and epigenetic risk factors for dental caries in children

Background Expenditure on dental and oral health services in Australia is $3.4 billion AUD annually. This is the sixth highest health cost and accounts for 7 % of total national health expenditure. Approximately 49 % of Australian children aged 6 years have caries experience in their deciduous teeth and this is rising. The aetiology of dental caries involves a complex interplay of individual, behavioural, social, economic, political and environmental conditions, and there is increasing interest in genetic predisposition and epigenetic modification. Methods The Oral Health Sub-study; a cross sectional study of a birth cohort began in November 2012 by examining mothers and their children who were six years old by the time of initiation of the study, which is ongoing. Data from detailed questionnaires of families from birth onwards and data on mothers’ knowledge, attitudes and practices towards oral health collected at the time of clinical examination are used. Subjects’ height, weight and mid-waist circumference are taken and Body Mass Index (BMI) computed, using an electronic Bio-Impedance balance. Dental caries experience is scored using the International Caries Detection and Assessment System (ICDAS). Saliva is collected for physiological measures. Salivary Deoxyribose Nucleic Acid (DNA) is extracted for genetic studies including epigenetics using the SeqCap Epi Enrichment Kit. Targets of interest are being confirmed by pyrosequencing to identify potential epigenetic markers of caries risk. Discussion This study will examine a wide range of potential determinants for childhood dental caries and evaluate inter-relationships amongst them. The findings will provide an evidence base to plan and implement improved preventive strategies.

Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients

Background Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. In this study we aim to identify DNA methylation changes associated with MS in CD8+ T cells in 30 relapsing remitting MS patients and 28 healthy blood donors using Illumina 450K methylation arrays. Findings Seventy-nine differentially methylated CpGs were associated with MS. The methylation profile of CD8+ T cells was distinctive from our previously published data on CD4+ T cells in the same cohort. Most notably, there was no major CpG effect at the MS risk gene HLA-DRB1 locus in the CD8+ T cells. Conclusion CD8+ T cells and CD4+ T cells have distinct DNA methylation profiles. This case–control study highlights the importance of distinctive cell subtypes when investigating epigenetic changes in MS and other complex diseases.

mRNA and microRNA analysis reveals modulation of biochemical pathways related to addiction in the ventral tegmental area of methamphetamine self-administering rats

Background Methamphetamine is a highly addictive central nervous system stimulant with increasing levels of abuse worldwide. Alterations to mRNA and miRNA expression within the mesolimbic system can affect addiction-like behaviors and thus play a role in the development of drug addiction. While many studies have investigated the effects of high-dose methamphetamine, and identified neurotoxic effects, few have looked at the role that persistent changes in gene regulation play following methamphetamine self-administration. Therefore, the aim of this study was to identify RNA changes in the ventral tegmental area following methamphetamine self-administration. We performed microarray analyses on RNA extracted from the ventral tegmental area of Sprague–Dawley rats following methamphetamine self-administration training (2 h/day) and 14 days of abstinence. Results We identified 78 miRNA and 150 mRNA transcripts that were differentially expressed (fdr adjusted p < 0.05, absolute log2 fold change >0.5); these included genes not previously associated with addiction (miR-125a-5p, miR-145 and Foxa1), loci encoding receptors related to drug addiction behaviors and genes with previously recognized roles in addiction such as miR-124, miR-181a, DAT and Ret. Conclusion This study provides insight into the effects of methamphetamine on RNA expression in a key brain region associated with addiction, highlighting the possibility that persistent changes in the expression of genes with both known and previously unknown roles in addiction occur.

Embodied energy in cement stabilised rammed earth walls

Rammed earth walls are low carbon emission and energy efficient alternatives to load bearing walls. Large numbers of rammed earth buildings have been constructed in the recent past across the globe. This paper is focused on embodied energy in cement stabilised rammed earth (CSRE) walls. Influence of soil grading, density and cement content on compaction energy input has been monitored. A comparison between energy content of cement and energy in transportation of materials, with that of the actual energy input during rammed earth compaction in the actual field conditions and the laboratory has been made. Major conclusions of the investigations are (a) compaction energy increases with increase in clay fraction of the soil mix and it is sensitive to density of the CSRE wall, (b) compaction energy varies between 0.033 MJ/m(3) and 0.36 MJ/m(3) for the range of densities and cement contents attempted, (c) energy expenditure in the compaction process is negligible when compared to energy content of the cement and (d) total embodied energy in CSRE walls increases linearly with the increase in cement content and is in the range of 0.4-0.5 GJ/m(3) for cement content in the rage of 6-8%. (C) 2009 Elsevier B.V. All rights reserved.

Performance modulation of α-MnO2 nanowires by crystal facet engineering

Modulation of material physical and chemical properties through selective surface engineering is currently one of the most active research fields, aimed at optimizing functional performance for applications. The activity of exposed crystal planes determines the catalytic, sensory, photocatalytic, and electrochemical behavior of a material. In the research on nanomagnets, it opens up new perspectives in the fields of nanoelectronics, spintronics, and quantum computation. Herein, we demonstrate controllable magnetic modulation of α-MnO 2 nanowires, which displayed surface ferromagnetism or antiferromagnetism, depending on the exposed plane. First-principles density functional theory calculations confirm that both Mn- and O-terminated α-MnO2(1 1 0) surfaces exhibit ferromagnetic ordering. The investigation of surface-controlled magnetic particles will lead to significant progress in our fundamental understanding of functional aspects of magnetism on the nanoscale, facilitating rational design of nanomagnets. Moreover, we approved that the facet engineering pave the way on designing semiconductors possessing unique properties for novel energy applications, owing to that the bandgap and the electronic transport of the semiconductor can be tailored via exposed surface modulations.

A dye-sensitized visible light photocatalyst-Bi24 O31 Cl10

The p-block semiconductors are regarded as a new family of visible-light photocatalysts because of their dispersive and anisotropic band structures as well as high chemical stability. The bismuth oxide halides belong to this family and have band structures and dispersion relations that can be engineered by modulating the stoichiometry of the halogen elements. Herein, we have developed a new visible-light photocatalyst Bi 24 O 31 Cl 10 by band engineering, which shows high dye-sensitized photocatalytic activity. Density functional theory calculations reveal that the p-block elements determine the nature of the dispersive electronic structures and narrow band gap in Bi 24 O 31 Cl 10. Bi 24 O 31 Cl 10 exhibits excellent visible-light photocatalytic activity towards the degradation of Rhodamine B, which is promoted by dye sensitization due to compatible energy levels and high electronic mobility. In addition, Bi 24 O 31 Cl 10 is also a suitable photoanode material for dye-sensitized solar cells and shows power conversion efficiency of 1.5%.